| Project/Area Number |
17590092
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyoritsu University of Pharmacy |
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Principal Investigator |
MASHINO Tadahiko Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Professor (90165697)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Shigeo Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Associate Professor (00264078)
TAKAHASHI Kyoko Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Assistant Professor (90255381)
NISHIZAWA Thiho Kyoritsu University of Pharmacy, Department of Pharmaceutical Sciences, Post doctoral fellow (50448990)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Fullerene / anti-cancer drug / and HIV drug / anti-hepatitis C virus drug / HIV reverse transcriptase / hepatitis C virus RNA polymerase / apoptosis / がん細胞増殖抑制 / HIV逆転写酵素阻害 / C型肝炎ウィルス増殖抑制 / がん細胞増殖抑制効果 / 抗菌活性 |
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| Research Abstract |
1. Cancer cell proliferation inhibition mechanism of fullerene derivatives.
It had already been reported that the pyrrolidinium type fullerene derivative (1) showed the cancer cell proliferation inhibition effect. We investigated the mechanism of inhibition using HL-60 cell line. Treatment of 1 induced the features of apoptosis and also induced the Caspase 3 and 9 activation and cytochromec release from mitochondria. But p53 induction was not observed. It is thought that the compound causes apoptosis without p53 induction is advantageous as the anti-cancer drug, because p53 is loss in cancer cells in many cases.
2. Design and synthesis of praline type fullerene derivatives with high HIV reverse transcriptase inhibition activity.
Using the computer docking simulation, various fullerene derivatives were designed and synthesized based on the structure of derivative (2) that had three carboxylic acids in the pyrrole ring. Relationship between the inhibition activity and number and position of carboxylic acid acids in the pyrrole ring was investigated and more active derivative 3 was developed. The inhibition activity of 3 was 100 times or more high than Nevirapin, which is used as and HIV drug.
3. Anti-hepatitis C virus activity of fullerene derivatives
Sulfonium type fullerene derivative (4) showed excellent hepatitis C virus RNA polymerase inhibition activity and hepatitis C virus growth inhibition activities. Cytotoxicity of 4 was low. 4 is a promising lead compound of the anti-hepatitis C virus medicine.
In this three years project, we developed the novel promising lead compounds for anti-cancer, anti-HIV, and anti-HCV medicine.
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